Differentiation between the stimulus effects of (+)-lysergic acid diethylamide and lisuride using a three-choice, drug discrimination procedure.
The discriminative stimulus properties of (+)-lysergic acid diethylamide (LSD) and lisuride hydrogen maleate (LHM), were compared in a three-choice, water reinforced (FR 20) situation in which rats were required to press one lever following LSD (0.08 mg/kg), a second lever following LHM (0.04 mg/kg), and a third lever following saline. Reliable drug-appropriate responding was established in 72 sessions. Dose-response tests with LSD and LHM indicated that, as dose increased, the per cent of responding on the lever associated with the particular training drug also increased; little or no cross-transfer occurred between LSD and LHM. In generalization tests, the serotonin (5-HT) agonist quipazine substituted for LSD but not LHM while the dopamine (DA) agonist apomorphine mimicked LHM but not LSD; an unrelated compound, pentylenetetrazol (PTZ), produced responding on the saline-appropriate lever. In combination tests, 5-HT antagonists (e.g., BC-105 and low doses of pirenperone) blocked responding on the LSD lever while DA antagonists (e.g., haloperidol and much higher doses of pirenperone) blocked LHM-appropriate responding. These data suggest that the three-lever (D-D-N) procedure is similar to, but can be more sensitive than the two-lever (D-N) procedure (because it can differentiate between LSD and LHM); they therefore at least partially support the hypothesis that three-choice discriminations can be conceptualized as two separate, two-choice (D-N) discriminations (Jarbe and Swedberg 1982). The results also confirm suggestion that the stimulus effects of LSD and LHM are mediated by different mechanisms; the primary action of LSD is serotonergic (5-HT2), while that of LHM is dopaminergic (White 1986).
Callahan
P M
PM
Department of Psychology, University of South Carolina, Columbia 29208.
Appel
J B
JB
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004873:Ergolines / Q000494:pharmacology*; D008090:Lisuride / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology
D004873:Ergolines; D012702:Serotonin Antagonists; D011814:Quipazine; D008238:Lysergic Acid Diethylamide; D008090:Lisuride; D001058:Apomorphine; D010433:Pentylenetetrazole